It is well established that aged male rats have reduced circulating concentrations of gonadotropin and testosterone, and reduced sperm number. We do not know whether age-related losses of spermatogenic cells results from changes in the hypothalamic-pituitary-Leydig cell axis alone or whether there also agree changes intrinsic to the spermatogenic cells themselves. Moreover, we know little of the effect of age on the endocrine requirements for restoring spermatogenic cells in experimentally regressed testes. This application proposes a series of quantitative experiments designed to examine the effects of defined changes in testosterone concentration within testicular compartments of cell proliferation, meiosis and spermatid differentiation in young and old rats; and on the replenishment of proliferating, meiotic an differentiating a cells in experimentally regressed rat testes The specific aims of the proposal are: 1)to determine whether decline in concentration within the interstitial and seminiferous tubular compartments of the testis, and/or from changes in the sensitivity of germ/Sertoli cells to the testosterone to which they are exposed; 2)to determine the numerical responses of specific proliferating, meiotic and differentiating cells throughout the testes of young and old rats to defined changes in intratesticular testosterone concentration; 3) to examine the effect of age and of testicular testosterone concentration on the replenishment of advanced spermatid and spermatozoa in experimentally regressed testes of young and old rats; 4) to examine the effect of intratesticular testosterone concentration on the extent to which specific spermatogonia, spermatocyte and early spermatid can be replenished in regressed testes of young and old rats; and 5) to determine the effect of intratesticular testosterone concentration on the extent to which advance spermatogenic cells can be restored in the regressed testes of old rats in which the seminiferous tubules have been experimentally isolated from the changes in pituitary LH and Leydig cell testosterone production that accompany normal aging. The overall goal of these studies is to determine how age affects the regulation of the ability of the rat testis to sustain or replenish normal complements of proliferating, meiotic and differentiating spermatogenic cells.